Quantitative phenotypic variation among individuals is ubiquitous for all measurable traits. Many inherited human diseases vary quantitatively in their expression, and furthermore natural selection operates on quantitative traits to shape phenotypic evolution. However, little is known of the underlying genetic basis of quantitative variation in phenotypes. The long-term goal of this project is to understand quantitative variation in terms of phenotypic and molecular variation of alleles at individual loci affecting them, using the numbers of abdominal and sternopleural bristles of Drosophila melanogaster as a model system. The immediate goals of this project are : (i) to conduct a comprehensive test of the hypothesis that quantitative variation for bristle number in natural populations is caused by naturally occurring alleles at loci known to affect bristle development and/or that have alleles with major effects on bristle number; (ii) to estimate quantitative genetic parameters (additive, dominance and pairwise epistatic effects, and pleiotropic effects of sex dimorphism and fitness) of small chromosomal regions containing naturally occurring and selected alleles at known bristle loci that have been introgressed into a common inbred background; and (iii) to determine to what extent genetic variation in phenotypes at these loci is associated with molecular polymorphisms. Factors causing response to selection for bristle number have been localized to small cytogenetic regions using polymorphic roo transposable element markers. To test whether naturally occurring alleles at candidate loci affecting bristle development located near these mapped factors have contributed to selection response, the factors will be introgressed into a common inbred background and tested for complementation with alleles and available deficiencies of the candidate loci. Additive, dominance, pairwise epistatic and sex-specific effects of the mapped factors will be estimated in the standard background. To further test the hypothesis that alleles at alleles at known bristle loci contribute to quantitative genetic variation in bristle number, the genetic variation in bristle number associated with approximately 50 naturally occurring alleles at each of 12 known bristle loci will be assessed, by introgressing the alleles into a standard inbred background by repeated backcrossing. For introgressed regions associated with significant variation in bristle number, heterozygous effects and pleiotropic effects on fitness will be estimated; pairwise epistatic effects will be assessed between introgressed regions containing wild type alleles at bristle loci with known genetic and molecular interactions; and restriction map and single strand conformation polymorphism will be determined. Associations between phenotypic variation and molecular polymorphisms will be assessed.